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Cervical cancer (CC) is the primary cancer-related cause of morbidity and mortality in women. Previous studies have shown that placenta-specific 8 (PLAC8) has different functions in multiple malignancies. This study aimed to explore the function and regulatory mechanism of PLAC8 in CC. Bioinformatics and immunohistochemical analyses demonstrated that PLAC8 was significantly upregulated in CC tissues compared with normal tissues. Gain/loss-of-function experiments showed that siRNA-mediated knockdown of PLAC8 suppressed cell migration and invasion, while PLAC8 overexpression promoted cell motility. Moreover, PLAC8 was revealed to affect the epithelial-mesenchymal transition (EMT) process by upregulating epithelial (E)-cadherin and decreasing the expression of mesenchymal markers of EMT, including vimentin, zinc finger E-box binding homeobox 1 (ZEB1), neural (N)-cadherin, matrix metalloproteinase-9 (MMP-9), and MMP-2 in PLAC8-silenced cells. PLAC8 activated the AKT pathway, as proven by the downregulation of p-AKT

The study relies on the provincial smart energy service platform of Jiangsu Province, optimizes its accurate prediction module of energy consumption and the energy efficiency improvement module, and proposes an efficiency improvement strategy based on the two modules of the platform. The accurate prediction module adopts the data processing and feature analysis method based on STL-MIC and builds a deep learning framework based on CNN-BiLSTM. The projected predicted data is then input to the energy efficiency improvement module, which employs the method of flexible load scheduling to achieve the best configuration of demand-side resources.

Cloud computing is popular in nowadays for its convenient and cheap. Grid provides services of available everywhere, and shares everyone. Therefore, smart grid cloud is a good way to manage data for sharing with all power supply stations. Grid cloud task scheduling is one of the key technologies that affect resource allocation efficiency in cloud computing environment. The advantages and disadvantages of scheduling algorithms will directly affect the scheduling performance of both cloud computing and the stability of the entire system platform. Cloud task scheduling problem has been proved to be a NP-hard problem, The traditional task scheduling algorithm can no longer meet the actual needs of cloud task scheduling, but the Heuristic algorithm is an effective method to solve this problem. This paper studies and analyzes the application of heuristic algorithms in cloud task scheduling problems, and proposes a cloud task scheduling strategy to minimize the task completion time and execution cost (MCTE) for the smart grid cloud. Then, carry out mathematical modeling on the grid cloud task scheduling problem. The experimental results show MCTE is well for the smart grid cloud.

As an efficient and reliable way of energy supply, the CCHP(Combined Cooling Heating and Power)microgrid can effectively realize the coordinated supply of a variety of energy sources. Based on the CCHP microgrid as the research object, using TRNSYS analysis building cooling and heating load characteristic, further analysis of distributed model of CCHP system, typical equipment system, establish a comprehensive cost saving rate, CO2 emission rate and a multi-objective optimization model of energy efficiency, using the NSGA - II algorithm system core equipment operation strategy and scheduling scheme. Taking a typical building load in northern China as an example, an example analysis of a building microgrid system with combined cooling, heating and power supply is carried out to verify the effectiveness of the optimization model and solving algorithm proposed in this paper. Results show that the CCHP microgrid based on multi-objective optimization algorithm can effectively implement the economic saving, reducing CO 2 emissions and enhance the utilization ratio of primary energy, further cost savings and protect the environment.

With the continuous advancement of urbanization, higher and higher requirements are put forward for infrastructure construction. Accurate fault diagnosis and timely maintenance of street lamps have become an important part of the lighting system. This paper proposes an intelligent fault diagnosis method for street lamps based illumination detection, narrowband Internet of Things (NB-IoT) technology and machine learning. In this proposed method, the narrowband IoT modules embedded with the illuminance sensor are installed and numbered at the street lamps and the collected illuminance data are uploaded to the server to build the illuminance database. Then the machine learning method is used to learn the modes of the collected data sequences and the street lamp turn-on models are constructed. Further, the real-time illuminance data sequence is processed to realize the fault diagnosis and to judge the fault type of a single street lamp or lamp group, and then feedback to the maintenance staff. To verify the proposed method, one example is also given. The proposed method provides one effective way for fault diagnosis of street lamps.

Adenomyosis is a benign uterus disease in which the invasion of the endometrial glands and/or stroma within myometrium is found and usually appears between the ages of 40 and 50 years in women. There are several differences in their pathogenesis. The secondary dysmenorrhea and menorrhagia are the common symptoms. Ultrasound sonography, MRI, CA125, and histological examination can be helpful for the diagnosis of adenomyosis. The treatment of adenomyosis depends on the patient’s age, symptoms, and desire for future fertility, including medical treatment and surgical treatment.

Although germline alterations and somatic mutations in disease cells have been extensively analyzed, molecular changes in immune cells associated with disease conditions have not been characterized in depth. It is clear that our immune system has a critical role in various biological and pathological conditions, such as infectious diseases, autoimmune diseases, drug-induced skin and liver toxicity, food allergy, and rejection of transplanted organs. The recent development of cancer immunotherapies, particularly drugs modulating the immune checkpoint molecules, has clearly demonstrated the importance of host immune cells in cancer treatments. However, the molecular mechanisms by which these new therapies kill tumor cells are still not fully understood. In this regard, we have begun to explore the role of newly developed tools such as next-generation sequencing in the genetic characterization of both cancer cells and host immune cells, a field that is called immunogenomics/ immunopharmacogenomics. This new field has enormous potential to help us better understand changes in our immune system during the course of various disease conditions. Here we report the potential of deep sequencing of T-cell and B-cell receptors in capturing the molecular contribution of the immune system, which we believe plays critical roles in the pathogenesis of various human diseases.

Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were in vitro expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of in vitro expanded populations in squamous cell carcinoma of head and neck (SCCHN) as well as their correlation with somatic mutations in cancer cells, we performed whole exome analysis, expression profile analysis of immune-related genes, and T cell receptor (TCR) analysis of original TILs and in vitro expanded TILs in 8 surgically-resected HPV-negative fresh tumors with SCCHN. We found an unusually high number of non-synonymous somatic mutations (4290, 1779 and 901 mutations) in three SCCHN tumors, in which we identified mutations in mismatch repair genes, MSH2 or MSH4, or a DNA polymerase gene, POLE. Interestingly, dominant TCR clonotypes of expanded CD8+ TILs derived from these three tumors revealed high similarity to those in original tumors while for remaining tumors with the lower mutational load, we found that T cell clonotypes between TILs in original tumor tissues and those expanded in vitro were almost entirely different. Our findings might provide clinically useful information for identification of tumor-antigen-specific T cell clones that may lead to further improvement of adoptive TIL therapy for SCCHN patients.

Cloud computing technology has become the most popular network technology. Therefore, it has been combined into grid, establishing smart grid cloud for independent data management of power supply stations. Smart grid cloud task scheduling is one of the key technologies that affect resource allocation efficiency in cloud computing environment. An improved particle swarm optimization-genetic algorithm cloud task scheduling strategy is proposed in this paper. The algorithm aims at minimizing the task completion time and execution cost, and carries out mathematical modeling on the cloud task scheduling problem. Coding the Particle in Particle Swarm Optimization Algorithm, and integrating the crossover and mutation operations of the genetic algorithm into the particle swarm algorithm so that the particle swarm algorithm can better solve the discrete problem. Finally, adding the precocious judgment and chaotic disturbance mechanism to the algorithm to help the algorithm jump out of the local optimum. The experimental results have shown the proposed strategy behaves well.

Energy storage refers to a series of related technologies that achieve energy reserve and release by some ways when needed. Energy storage technology plays an important role in peak shaving and valley filling, improving the equipment utilization efficiency, enhancing the system safety and so on. It has great significances to realize the transformation of energy structure and the change of electricity production or consumption patterns for promoting the overall development of energy industry through the research of user-side energy storage technology. In this paper, we analyze the historical power consumption data of industrial users by K-Means clustering algorithm to design a user type automatic evaluation model, which can assist large industrial users to judge whether industrial users are suitable for energy storage construction or not, it can help enterprises save manpower and financial resources. In addition, we design a method to calculate the potential value of users, which can reflect the degree of suitability for equipping energy storage device. Simulation results show that the proposed model can correctly obtain the users’ typical load curve and power usage type through clustering historical power load data.

To develop a practically applicable method for T-cell receptor (TCR)-engineered T cell immunotherapy targeting neoantigens, we have been attempting to identify neoantigen-specific T cell receptors (TCRs) and establish TCR-engineered T cells in a 3–4-month period. In this study, we report the characterization of T cell repertoires in tumor microenvironment (TME) and identification of neoantigen-specific TCRs after stimulation of patient-derived T cells. We screened 15 potential neoantigen peptides and successfully identified two CD8+HLA-dextramer+ T cells, which recognized MAGOHBG17A and ZCCHC14P368L. All three dominant TCR clonotypes from MAGOHBG17A-HLA dextramer-sorted CD8+ T cells were also found in T cells in TME, while none of dominant TCR clonotypes from ZCCHC14P368L-HLA dextramer-sorted CD8+ T cells was found in the corresponding TME. The most dominant TCRA/TCRB pairs for these two neoantigens were cloned into HLA-matched healthy donors’ T lymphocytes to generate TCR-engineered T cells. The functional assay showed MAGOHBG17A TCR-engineered T cells could be significantly activated in a mutation-specific, HLA-restricted and peptide-dose-dependent manner while ZCCHC14P368L TCR-engineered T cells could not. Our data showed neoantigen-reactive T cell clonotypes that were identified in the patient’s peripheral blood could be present in the corresponding TME and might be good TCRs targeting neoantigens.

Utilizing biological components for data transfer is considered as a promising technique for communications at nanoscales. The ability to store data in its DNA strands as well as natural mobility make flagellated bacteria a good candidate for such systems. The use of advanced mechanisms such as replication-based encoding and conjugation to improve the performance of bacterial nanonetworks as well as stochastic bacteria movement pattern make their performance assessment a non-trivial task. Universal analytical frameworks taking into account these mechanisms are still missing. The situation is complicated by the possibility of having more than a single transmitter–receiver (Tx–Rx) pair communicating in the environment of interest. In this paper, we develop a framework to characterize performance of the bacterial networks taking all the abovementioned mechanisms into account and capable to address the case of simultaneous communications between a number of Tx–Rx pairs. The framework is based on the absorbing Markov chains theory and allows to reveal inherent trade-offs related to delay performance of bacterial nanonetworks.

Alteration of protein O-glycosylation in various human cancers including breast cancer is well known, but molecular roles of their aberrant glycosylations on cancer have not been fully understood. We previously reported critical roles of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6 or GalNAc-T6) that was upregulated in a great majority of breast cancer tissues. Here we further report O-glycosylation of estrogen receptor alpha (ER-α) by GALNT6 and the significant role of its nuclear localization in breast cancer cells. Knockdown of GALNT6 expression in two breast cancer cell lines, T47D and MCF7, in which both ER-α and GALNT6 were highly expressed, by small interfering RNA could significantly attenuate expression of ER-α. Immunocytochemical analysis clearly demonstrated the drastic decrease of ER-α protein in the nucleus of these cancer cells. Accordingly, the downstream genes of the ER-α pathway such as MYC, CCND1, and CTSD were significantly downregulated. We confirmed GALNT6-dependent ER-α O-glycosylation and identified O-glycosylation of S573 in an F domain of ER-α by GALNT6 through LC-MS/MS analysis. We also obtained evidences showing that the glycosylation of ER-α at S573 by GALNT6 is essential for protein stability and nuclear localization of ER-α in breast cancer cells. Furthermore, we designed cell membrane–permeable peptides including the O-glycosylation site and found a significant decrease of the cell viability of breast cancer cells by treatment of these peptides in a GALNT6 expression–dependent manner. Our study suggests that targeting the GALNT6 enzymatic activity as well as the GALNT6/ER-α interaction could be a promising therapeutic approach to ER-α–positive breast cancer patients.

Tumor-associated macrophages (TAMs) are correlated with poor prognosis in many human cancers; however, the mechanism by which TAMs facilitate ovarian cancer cell migration and invasion remains unknown. This study was aimed to examine the function of adrenomedullin (ADM) in macrophage polarization and their further effects on the migration of ovarian cancer cells. Exogenous ADM antagonist and small interfering RNA (siRNA) specific for ADM expression were treated to macrophages and EOC cell line HO8910, respectively. Then macrophages were cocultured with HO8910 cells without direct contact. Flow cytometry, Western blot and real-time PCR were used to detect macrophage phenotype and cytokine production. The migration ability and cytoskeleton rearrangement of ovarian cancer cells were determined by Transwell migration assay and phalloidin staining. Western blot was performed to evaluate the activity status of signaling molecules in the process of ovarian cancer cell migration. The results showed that ADM induced macrophage phenotype and cytokine production similar to TAMs. Macrophages polarized by ADM promoted the migration and cytoskeleton rearrangement of HO8910 cells. The expression of RhoA and its downstream effector, cofilin, were upregulated in macrophage-induced migration of HO8910 cells. In conclusion, ADM could polarize macrophages similar to TAMs, and then polarized macrophages promote the migration of ovarian cancer cells via activation of RhoA signaling pathway in vitro.

Neoantigen-reactive T cells are considered to be crucial mediators for anti-tumor activity in adoptive T cell transfer (ACT) immunotherapy although the efficacy of ACT using in vitro expanded tumor-infiltrating T lymphocytes (TILs) has been limited. Since characterization of T cell receptor (TCR) repertoires of TILs before and after in vitro expansion has not well investigated, we in present study performed whole exome sequencing (WES) and transcriptome analysis, and selected candidate neoantigen epitopes to induce cytotoxic T lymphocytes (CTLs) in 20 patients with head and neck cancer (10 frozen tissues and 10 freshly resected tumors). 36 potential neoantigen peptides including missense somatic mutations were examined for induction of neoantigen-reactive cytotoxic T cells in vitro using patients' derived dendritic cells. We have so far confirmed three neoantigen-reactive T cells and obtained the sequence information of a pair of TCR alpha and beta chains, which were identical to those identified in resident dominant TILs in the original tumors. We cloned the TCR genes into T lymphocytes and constructed the neoantigen-reactive T-cell receptor-engineered (TCR-engineered) T cells, which showed HLA-restricted neoantigen-reactive cytotoxic activity. In addition, we compared the TCR composition of TILs before/after in vitro expansion in 10 fresh head and neck cancers, and found that TCR clonotypes in original TILs and in vitro expanded TILs are drastically different except for those between expanded CD8 cells and resident TILs in three tumors, which had unusually high mutational burden due to mutations in the mismatch repair genes (MSH2, MSH6) or a DNA polymerase (POLE) gene. Our data also suggest that some expanded TILs are likely to be cancer-specific T cells and may be good cell sources for ACT immunotherapy and that the mutational load might be a good biomarker to screen effective TIL treatment. We demonstrate establishment of an effective and rapid protocol to generate neoantigen-specific T cells and to identify neoantigen-specific TCRs for individual patients, which makes TCR-engineered T cells applicable for the clinical use. Citation Format: Lili Ren, Tatsuo Matsuda, Boya Deng, Kazuma Kiyotani, Taigo Kato, Jae-Hyun Park, Tanguy Seiwert, Everett Vokes, Nishant Agrawal, Yusuke Nakamura. Screening of neoantigen-specific T cells in head and neck cancer and establishment of T-cell receptor-engineered T cells with cytotoxic reactivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 963.

Alteration of protein O-glycosylation in various human cancers including breast cancer is well known, but molecular mechanisms of such aberrant modifications and their effects on cancer development have not been fully understood. We previously reported the critical roles of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which is upregulated in a great majority of breast cancers and is responsible for initiating mucin-type O-glycosylation. Suppression of GALNT6 expression by small interfering RNA to GALNT6 significantly enhanced cell-cell adhesion, induced mesenchymal-epithelial transition, and suppressed the growth of breast cancer cells. Here we further analyzed molecular functions of GALNT6 and found that GALNT6 could glycosylate an estrogen receptor alpha (ER-α) protein, a molecule playing a central role in proliferation of hormone-dependent breast cancer cells. We have used two breast cancer cell lines, T47D and MCF7, in which both the estrogen receptor and GALNT6 were highly expressed. Knockdown of GALNT6 expression by siRNA could significantly attenuate expression of ER-α at transcriptional and protein levels in these breast cancer cell lines in a condition with or without estradiol (P Citation Format: Boya Deng, Yunus Emre Tarhan, Koji Ueda, Yo Matsuo, Jae-Hyun Park, Yusuke Nakamura. Glycosylation of estrogen receptor alpha by N-acetylgalactosaminyltransferase 6 in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 977.

e16529Background: Bladder cancer is the fourth most common cancer in males and the 11th most common in females, with a projected 81,190 new cases and 17,240 deaths in the USA in 2018.Anti-PD1 check...

Background Anti–programed cell death 1 checkpoint inhibitors have recently demonstrated effectiveness against metastatic cancers including urothelial carcinoma. Aims To identify biomarkers/factors that correlate with the clinical response in advanced bladder cancer patients who received immune checkpoint inhibitor treatment. Methods and results We investigated tumors from 18 bladder cancer patients who had received anti–programed cell death 1 (pembrolizumab) or anti–programmed death‐ligand 1 therapy (atezolizumab or durvalumab) and performed exome analysis, T‐cell receptor sequencing of the tumor‐infiltrating lymphocytes (TILs), and immunohistochemical analysis of CD8 and programmed death‐ligand 1 in cancer tissues. Immunohistochemical analysis of bladder cancer tissues demonstrated that a higher number of CD8 T‐cell infiltration into cancer tissues was significantly associated with longer cancer‐specific survival of the patients (P = .0012). T‐cell receptor beta sequencing of TILs using genomic DNAs extracted from the tissues of 15 cases revealed that patients with higher clonal expansion of TILs had some tendency of longer cancer‐specific survival (P = .055), than those with lower clonal expansion. We performed whole exome sequencing of 14 cases and found that patients carrying higher numbers of somatic mutations received greater benefit from immunotherapy (P = .034) and one patient who had high microsatellite instability has survived for 1034 days. Conclusion CD8 infiltration in tumors and nonsynonymous mutation load might be useful predictive markers for immune checkpoint inhibitors for bladder cancer patients.

Dysregulation of microRNAs (miRNAs) occurs frequently in cervical carcinogenesis. miRNAs function as tumor-suppressors or oncogenes and are involved in tumor behavior. However, the expression and function of miR-27b in cervical carcinogenesis remain unknown. In the present study, we observed that miR-27b was significantly increased in cervical cancer cells and tissues, and upregulation of miR-27b was negatively associated with its direct target, cadherin 11 (CDH11). Upregulation of miR-27b significantly accelerated the proliferation, cell cycle transition from G1 to S phase, migration and invasion of C33A cells, while downregulation of miR-27b suppressed the proliferation and invasion of HeLa cells. Moreover, CDH11 cDNA transfection impaired the oncogenic effect of miR-27b on cancer cells. Knockdown of CDH11 attenuated the suppressive effect of an miR-27b inhibitor on cervical cancer cells. In addition, we found that CDH11 was involved in miR-27b-induced epithelial-mesenchymal transition (EMT) by regulating expression of E-cadherin, vimentin and N-cadherin. Our results for the first time indicate that miR-27b acting as an oncogene may play an important role in the progression of cervical cancer by modulating CDH11 and EMT.

Frizzled-7 (FZD7) has been demonstrated as a critical receptor of the Wnt signaling and involves in tumorigenesis and metastasis in many cancer types. However, limited information was found in cervical cancer. The aim of this study was to investigate the functional role of FZD7 in migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. HeLa and SiHa cervical carcinoma cell lines with FZD7 expression were chosen in this study. A short hairpin RNA (shRNA) construct targeting FZD7 mRNA was transfected into HeLa and SiHa cells, and the stably transfected cell lines were obtained through G418 screening. Functional experiments were further performed to assess whether FZD7 down-regulation affects the migration, invasion, and EMT of HeLa and SiHa cells. Our results revealed that down-regulation of FZD7 expression significantly inhibited cell invasion and migration, as well as decreased the expression and activities of MMP2 and MMP9 in both cell types. Additionally, FZD7 silencing resulted in down-regulation of mesenchymal markers including Vimentin and Snail while increased the levels of epithelial marker E-cadherin. We further found that decreased FZD7 expression inhibited the phosphorylation levels of JNK and c-jun in both HeLa and SiHa cells, as determined by Western blot analysis and immunofluorescence. Overall, our results indicate that shRNA-mediated knockdown of FZD7 inhibits invasion, metastasis, and EMT of cervical cancer cells. FZD7 may provide a promising therapeutic target in cervical cancer.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles in tumorigenesis and tumor progression through regulation of gene expression. Earlier, miR-142-3p was shown to decreased in cervical cancer cells; here; we explore the biological functional role of miR-142-3p and underlying mechanism in cervical cancer cells. We first detected the expression of miR-142-3p in six human cervical cancer cell lines and chose HeLa and SiHa cells for functional studies. By gain and loss of function experiments, we showed that overexpression of miR142-3p resulted in downregulation of Frizzled7 receptor (FZD7) and inhibited proliferation and invasion in HeLa and SiHa cells, whereas miR142-3p inhibitor-transfected cells showed reduced FZD7 expression and increased invasion capacity. In addition, we demonstrated that FZD7 was a direct target of miR-142-3p by dual luciferase assay and Western blot analysis. Overexpression of FZD7 expression was able to reverse the inhibitory effects induced by miR-142-3p. Taken together, miR-142-3p functions tumor suppressive effects in cell proliferation and invasion in cervical cancer cells, suggesting a potential therapeutic approach for cervical cancer.

B-cell translocation gene 3 (BTG3) is a member of the BTG family which inhibits cell proliferation, metastasis, and angiogenesis, and also regulates cell-cycle progression and differentiation in a variety of cell types. However, there is no study to analyze BTG3 expression in epithelial ovarian carcinoma (EOC). Here, we investigated the expression of BTG3 in EOC carcinogenesis and subsequent progression. BTG3 mRNA expression was detected by real-time RT–PCR in ovarian benign and malignant tumors. The expression of BTG3 protein was examined by immunohistochemistry on tissue microarrays containing ovarian normal tissue, benign and borderline epithelial ovarian tumors, and EOCs. Relationships of BTG3 with both EOC clinicopathology and prognosis were analyzed statistically. The expression of BTG3 protein was also evaluated in ovarian normal tissue, benign tumors, and EOCs by western blot. The BTG3 mRNA expression level was higher in ovarian normal tissue and benign tumors than that in borderline, primary, and metastatic carcinoma (p